Review
Immunology
Liang Ren, Daonan Shen, Chengcheng Liu, Yi Ding
Summary: The oral cavity contains a wide range of microbial species, and imbalanced microbiota-host interactions are responsible for various oral diseases. Recent studies have shown that bacterial protein phosphorylation plays a crucial role in oral bacterial dysbiosis and bacteria-host interactions, and ongoing research aims to uncover the underlying mechanisms.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Article
Multidisciplinary Sciences
Kyle W. Bender, Daniel Couto, Yasuhiro Kadota, Alberto P. Macho, Jan Sklenar, Paul Derbyshire, Marta Bjornson, Thomas A. DeFalco, Annalise Petriello, Maria Font Farre, Benjamin Schwessinger, Vardis Ntoukakis, Lena Stransfeld, Alexandra M. E. Jones, Frank L. H. Menke, Cyril Zipfel
Summary: Receptor kinases are key in extracellular sensing and stress responses in plants, with leucine-rich repeat receptor kinases regulating responses to internal and external stimuli. The phosphorylation of cytoplasmic domains is crucial for activating RK complexes, but it is not a ubiquitous requirement for LRR-RK activation. Further studies on different protein kinase domains may provide insights into the regulation of LRR-RK complexes.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Oncology
Xinyan Wu, Li Wang, Nicole A. Pearson, Santosh Renuse, Ran Cheng, Ye Liang, Dong-Gi Mun, Anil K. Madugundu, Yaoyu Xu, Parkash S. Gill, Akhilesh Pandey
Summary: This study utilized mass spectrometry-based proteomics to quantify cancer signaling regulated by AXL activation, identifying over 1000 phosphotyrosine sites and upregulation of cancer-promoting and cell migration pathways. Rapid phosphorylation of multiple receptor tyrosine kinases and protein tyrosine phosphatases was observed upon GAS6 stimulation. The study provides insights into AXL's oncogenic role and potential therapeutic targets.
Article
Cell Biology
Zhe Qian, Dongyan Song, Jonathan J. Ipsaro, Carmelita Bautista, Leemor Joshua-Tor, Johannes T. -H. Yeh, Nicholas K. Tonks
Summary: In this study, the researchers generated a novel monoclonal antibody, RD-43, which targeted the ectodomain of PTPRD to inhibit its function and promote its degradation. Treatment with RD-43 was found to suppress SRC signaling required for breast cancer cell invasion. These findings suggest that antibodies targeting extracellular segments of receptor protein tyrosine phosphatases may have therapeutic potential.
GENES & DEVELOPMENT
(2023)
Review
Cell Biology
Michel L. Tremblay
Summary: In this study, a monoclonal antibody targeting PTPRD was identified, which induced dimerization and inhibition of the phosphatase activities of PTPRD and led to its proteolysis by intracellular degradation pathways. This finding opens up a new framework for the clinical manipulation of PTPRD and its closely related family members.
GENES & DEVELOPMENT
(2023)
Article
Biochemistry & Molecular Biology
Idil Ulengin-Talkish, Martha S. Cyert
Summary: Intracellular Ca2+ signals are controlled and limited in time and space. Calcineurin, a Ca2+/calmodulin regulated protein phosphatase, plays versatile roles throughout the cell by forming signaling microdomains where calcium-dependent effectors and substrates co-localize. This review summarizes the function of calcineurin, with a focus on the localization and targeting mechanisms, particularly the binding of short linear peptide motifs (SLiMs). Calcineurin regulates events at various cellular locations, including plasma membrane, intracellular membranes, mitochondria, nuclear pore complex and centrosomes/cilia, as revealed by the systematic mapping of its substrates and regulators.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
(2023)
Article
Biology
Payam E. Farahani, Xiaoyu Yang, Emily Mesev, Kaylan A. Fomby, Ellen H. Brumbaugh-Reed, Caleb J. Bashor, Celeste M. Nelson, Jared E. Toettcher
Summary: pYtags is a modular approach for monitoring the activity of a specific RTK by live-cell microscopy. It enables monitoring of a specific RTK on different time and space scales with high specificity. Using pYtag biosensors, signaling dynamics can be quantitatively characterized with different activating ligands. The specificity and modularity of pYtags open the door to robust biosensors of multiple tyrosine kinases.
Review
Immunology
Frederic Bornancin, Carien Dekker
Summary: This review focuses on the regulation of the NLRP3 inflammasome by phosphorylation and dephosphorylation, and discusses the kinases and phosphatases that have been reported to modulate NLRP3 activity. The aim is to integrate the current understanding and highlight potential gaps for further studies.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Julia Kamenz, Lendert Gelens, James E. Ferrell
Summary: The phosphorylation of mitotic proteins is bistable, regulated by both Cdk1 and PP2A-B55 in a bidirectional manner. The changes in PP2A-B55 activity serve as the ultimate trigger for mitotic entry and exit, indicating its crucial role in regulating cell cycle progression.
Article
Multidisciplinary Sciences
Maximilian Mosbacher, Sung Sik Lee, Gilad Yaakov, Mariona Nadal-Ribelles, Eulalia de Nadal, Frank van Drogen, Francesc Posas, Matthias Peter, Manfred Claassen
Summary: This study characterizes the regulation of MAP kinase Hog1 in Saccharomyces cerevisiae and reveals a mixed phosphorylation mechanism regulated by a positive feedback loop. Simulations show that this mechanism is necessary for full sensitivity to stimuli and robustness to perturbations.
NATURE COMMUNICATIONS
(2023)
Article
Chemistry, Analytical
Ke Xiao, Rong Zhu, Cuicui Du, Hejie Zheng, Xiaohua Zhang, Jinhua Chen
Summary: A self-powered photoelectrochemical (PEC) sensor using zinc-air batteries as a power source was developed for activity assay of protein tyrosine phosphatase 1B (PTP1B). The sensor showed superior performance with a broad linear response range and low detection limit, indicating great potential in the diagnosis of protein phosphatase-related diseases and the development of targeted drugs.
ANALYTICAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Evangelia Papadimitriou, Vasiliki K. Kanellopoulou
Summary: Protein tyrosine phosphatase receptor zeta 1 (PTPRZ1) is highly expressed during embryonic development but limited in adulthood. It plays a role in oligodendrocytes' survival and maturation in the central nervous system. In gliomas, PTPRZ1 is significantly upregulated and studied as a potential cancer driver and therapy target. However, its functional significance and tumor-suppressor role in other cancer types need further investigation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Multidisciplinary Sciences
Danielle L. Schmitt, Stephanie D. Curtis, Anne C. Lyons, Jin-fan Zhang, Mingyuan Chen, Catherine Y. He, Sohum Mehta, Reuben J. Shaw, Jin Zhang
Summary: AMP-activated protein kinase (AMPK) is a master regulator of cellular metabolism. Researchers have developed a sensitive biosensor for AMPK and used it to uncover mechanisms for AMPK activity in the lysosome and nucleus.
NATURE COMMUNICATIONS
(2022)
Article
Cell Biology
Kun Zhou, Qiaoli Chen, Jiamou Chen, Derong Liang, Weikuan Feng, Minjun Liu, Qi Wang, Ruizhen Wang, Qian Ouyang, Chao Quan, Shuai Chen
Summary: This study reveals the critical role of liquid-liquid phase separation (LLPS) in the spatiotemporal control of insulin signaling. LLPS regulates multiple components, including IRS1, and is involved in the formation of intracellular IRS1 condensates. Insulin stimulation and protein concentration drive the formation of IRS1 condensates, which function as intracellular signal hubs for insulin signaling. Impairment of IRS1 condensate formation is observed in insulin resistant cells. Overall, LLPS plays an important role in the regulation of insulin signaling.
Article
Cell Biology
Stephanie M. Stanford, Meghan Collins, Michael A. Diaz, Zachary J. Holmes, Paul Gries, Matthew R. Bliss, Alessia Lodi, Vida Zhang, Stefano Tiziani, Nunzio Bottini
Summary: LMPTP plays a key role in adipocyte differentiation by regulating PDGFRα signaling and affecting multiple pathways involved in fat cell growth, differentiation, and glucose utilization in adipose tissue.
JOURNAL OF CELLULAR PHYSIOLOGY
(2021)
Article
Neurosciences
Sophie Longueville, Yuki Nakamura, Karen Brami-Cherrier, Renata Coura, Denis Herve, Jean-Antoine Girault
Summary: The researchers introduced a novel mouse line, Egr1-CreER(T2), to permanently tag activated neurons. These tagged neurons can be activated and studied under specific experimental conditions, such as epileptic seizures or cocaine administration. Additionally, the study showed that cocaine-induced tagging required ERK activation and the tagged neurons were more likely to exhibit certain molecular changes after a second injection.
EUROPEAN JOURNAL OF NEUROSCIENCE
(2021)
Biographical-Item
Biochemistry & Molecular Biology
Jean-Antoine Girault, Bernard Scatton, Michel Hamon
Summary: Dr. Jacques Glowinski, a founding father of neuropharmacology in France, trained generations of students at his famous laboratory in Paris and made important scientific contributions to the regulatory mechanisms of central dopaminergic neurotransmission.
JOURNAL OF NEUROCHEMISTRY
(2021)
Editorial Material
Medicine, Research & Experimental
Emma Puighermanal, Laia Castell, Jean-Antoine Girault, Emmanuel Valjent
M S-MEDECINE SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Benoit Forget, Elena Martin Garcia, Arthur Godino, Laura Domingo Rodriguez, Vincent Kappes, Pierre Poirier, Andry Andrianarivelo, Eric Senabre Marchan, Marie-Charlotte Allichon, Melanie Marias, Peter Vanhoutte, Jean-Antoine Girault, Rafael Maldonado, Jocelyne Caboche
Summary: The study shows that certain miRNAs are preferentially upregulated in the NAc after sustained cocaine exposure and miR-1 overexpression in specific striatal cell populations can affect cocaine-induced behaviors by reducing reinstatement and motivation in a cell-type specific manner.
MOLECULAR PSYCHIATRY
(2022)
Article
Biochemistry & Molecular Biology
Enrica Montalban, Albert Giralt, Lieng Taing, Evelien H. S. Schut, Laura F. Supiot, Laia Castell, Yuki Nakamura, Benoit de Pins, Assunta Pelosi, Laurence Goutebroze, Pola Tuduri, Wei Wang, Katrina Daila Neiburga, Letizia Vestito, Julien Castel, Serge Luquet, Angus C. Nairn, Denis Herve, Nathaniel Heintz, Claire Martin, Paul Greengard, Emmanuel Valjent, Frank J. Meye, Nicolas Gambardella, Jean-Pierre Roussarie, Jean-Antoine Girault
Summary: Forebrain dopamine-sensitive neurons play important roles in movement, action selection, motivation, and working memory. This study compares different populations of dopaminoceptive neurons and identifies differences in gene expression between them. Additionally, it reveals the potential role of prostaglandin E2 as a neuromodulator in the striatum and a potential therapeutic target.
MOLECULAR PSYCHIATRY
(2022)
Article
Chemistry, Multidisciplinary
Anna-Katharina Mueller, Ulrike A. Koehler, Sebastien Trzebanski, Yaron Vinik, Harsha Mohan Raj, Jean-Antoine Girault, Nir Ben-Chetrit, Antonio Maraver, Steffen Jung, Sima Lev
Summary: This study finds that macrophage infiltration in mammary tumors is associated with tumor progression, metastasis, and poor clinical outcome. Ablation of the TYRO3 kinase PYK2 can reduce the number of infiltrating macrophages, inhibit tumor angiogenesis and growth, and modulate monocyte recruitment, macrophage polarization, and tumor angiogenesis. Targeting PYK2 may be an effective strategy to modulate the tumor microenvironment and sensitize breast cancer to immunotherapy.
Article
Neurosciences
Veronica Brito, Enrica Montalban, Anna Sancho-Balsells, Anika Pupak, Francesca Flotta, Merce Masana, Silvia Gines, Jordi Alberch, Claire Martin, Jean-Antoine Girault, Albert Giralt
Summary: Motor skills learning is associated with cerebral and cerebellar cortices, basal ganglia nuclei, and now also found to involve the hippocampus. Transcriptional changes and reduced activity of pyramidal neurons in the CA1 region of the hippocampus are observed in mice trained in the accelerating rotarod. A subpopulation of Egr1-expressing pyramidal neurons in CA1 is activated during short-term and long-term training in the rotarod task. Manipulations of Egr1 or these neuronal ensembles affect motor learning performance, showing the importance of the hippocampus in controlling motor skill learning.
JOURNAL OF NEUROSCIENCE
(2022)
Article
Cell Biology
Laura Lopez-Molina, Joaquin Fernandez-Irigoyen, Carmen Cifuentes-Diaz, Jordi Alberch, Jean-Antoine Girault, Enrique Santamaria, Silvia Gines, Albert Giralt
Summary: This study explores the function of Pyk2 in mitochondria-associated membranes (MAMs) and demonstrates its role in regulating ER-mitochondria calcium efflux, affecting mitochondrial function and leading to calcium homeostasis imbalance.
Article
Biology
Afaque A. Momin, Tiago Mendes, Philippe Barthe, Camille Faure, SeungBeom Hong, Piao Yu, Gress Kadare, Mariusz Jaremko, Jean-Antoine Girault, Lukasz Jaremko, Stefan T. Arold
Summary: This study investigates the mechanism of how PYK2 functions as a sensor and effector of cellular calcium influx. It identifies a calmodulin binding element in the linker between the PYK2 kinase and FAT domains. The results show that calcium influx promotes PYK2 self-association, leading to kinase activation.
COMMUNICATIONS BIOLOGY
(2022)
Article
Neurosciences
Jean-Antoine Girault
Summary: Limited reproducibility and validity are major concerns in biology and other scientific fields. The author proposes a simple solution where scientists deposit their positive or negative results in a database, which are then validated and open to public access, in order to improve the transparency and reliability of scientific publications.
Article
Biology
Lucile Marion-Poll, Jean-Pierre Roussarie, Lieng Taing, Cloelia Dard-Dascot, Nicolas Servant, Yan Jaszczyszyn, Emmanuelle Jordi, Eskeatnaf Mulugeta, Denis Herve, Deborah Bourc'his, Paul Greengard, Claude Thermes, Jean-Antoine Girault
Summary: Neuronal DNA modifications, including methylation outside CpG context and abundant 5-hydroxymethylation, show distinct patterns in striatal projection neurons expressing D1 or D2 dopamine receptors. DNA methylation differences mainly occur in large genomic clusters related to differentially expressed genes, while hydroxymethylation differences are scattered and affect transcription factor binding sites.
COMMUNICATIONS BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Anna Sancho-Balsells, Sara Borras-Pernas, Veronica Brito, Jordi Alberch, Jean-Antoine Girault, Albert Giralt
Summary: Chronic stress can lead to neurological disorders, such as major depression, and affects the hippocampus, leading to functional changes. The transcription factor Egr1 plays a role in hippocampal function but its involvement in stress-induced effects is not well understood. This study used mice and found that stress protocols induced activation or deactivation of hippocampal CA1 neural ensembles, along with dendritic spine pathology, in an Egr1-dependent manner. Manipulating superficial pyramidal neurons in the hippocampus resulted in the amelioration of depressive-like behaviors and cognitive impairments caused by chronic stress.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
Lucas Blasquez, Haniaa Bouzinba-Segard, Sandrine Bourdoulous, Camille Faure
Summary: Human epidermal growth factor receptor 2 (HER2) is overexpressed in various cancers, including breast cancer, and targeted therapies have shown benefits. However, resistance mechanisms and toxicity call for new approaches. This study identified ebselen oxide as an allosteric inhibitor of HER2, which efficiently inhibited overexpressed and resistant forms of HER2. Ebselen oxide selectively inhibited proliferation and showed synergy with current anti-HER2 therapies. It also blocked tumor progression in vivo. These findings suggest ebselen oxide as a potential therapeutic option for HER2-positive cancers.
MOLECULAR ONCOLOGY
(2023)
Article
Neurosciences
Monica Pardo, Sara Gregorio, Enrica Montalban, Lluis Pujadas, Alba Elias-Tersa, Nuria Masachs, Alba Vilchez-Acosta, Annabelle Parent, Carme Auladell, Jean-Antoine Girault, Miquel Vila, Angus C. C. Nairn, Yasmina Manso, Eduardo Soriano
Summary: Reelin protein is implicated in psychiatric disorders, but its effects on the structure and neuronal composition of the striatum are not well understood. This study found that overexpression of Reelin protein increases the numbers of striatal interneurons and cholinergic neurons, and slightly increases the tyrosine hydroxylase-positive projections from the substantia nigra to the striatum. These findings suggest that increased levels of Reelin may protect against neuropsychiatric disorders by modifying these structures and neuronal numbers.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2023)